Hyposalivation, or an abnormally low salivary flow rate, is a major health problem associated with coronal and root surface dental caries, and a profound reduction in quality of life despite best clinical practices. Medications are the most common cause of chronic hyposalivation. A second major cause of chronic hyposalivation is Sj?gren's Syndrome, one of the most prevalent autoimmune disorders in the developed world. The microbiota of the exposed tooth surface plays a critical role in caries formation. In order to reduce the burden of caries and tooth loss in these populations, we propose to identify shifts in the composition of the microbiota that are associated with the acute and chronic states of hyposalivation and the subsequent development of caries. Detection of early diagnostic changes in the microbiota will facilitate early therapeutic intervention. Although many culture-based studies have examined the impact of hyposalivation on oral microbial communities, none have examined spatially explicit impacts at distinct supragingival sites over time. Furthermore, cultivation provides a limited view of bacterial diversity and community structure. Our preliminary, sequencing-based data show that the taxonomic composition of supragingival plaques varies between and across teeth in the absence of hyposalivation. This finding, combined with the observation that the distribution of caries shifts in a site-specific manner to the incisors and canines in states of hyposalivation, suggests that we need to examine spatiotemporal variation in supragingival communities in the absence and presence of hyposalivation if we are to understand (and ultimately prevent) the progression from health- associated to hyposalivation- and caries-associated community states. This Application addresses this need by defining and characterizing population-level transitions and differences in supragingival microbial communities at multiple spatial and temporal scales in health and in acute and chronic states of hyposalivation. Aim 1: Characterize the spatiotemporal dynamics of the supragingival and salivary microbiota in healthy adults in the absence of hyposalivation. Aim 2: Characterize acute impacts of medication-induced hyposalivation on the supragingival and salivary microbiota of healthy adults. Aim 3: Evaluate impact of chronic hyposalivation on the supragingival and salivary microbiota in patients with Sj?gren's Syndrome. Our long-term objectives are to develop new diagnostic markers for hyposalivation-associated cariogenic microbial communities, as well as to develop novel ecologically-based therapeutics to decrease dental caries incidence in high risk patients, and to understand better the role of microbial communities in cariogenesis.